CN105111206B - A kind of cyclopropanecarbonyl amine derivative crystal form E and preparation method thereof - Google Patents
A kind of cyclopropanecarbonyl amine derivative crystal form E and preparation method thereof Download PDFInfo
- Publication number
- CN105111206B CN105111206B CN201510598698.6A CN201510598698A CN105111206B CN 105111206 B CN105111206 B CN 105111206B CN 201510598698 A CN201510598698 A CN 201510598698A CN 105111206 B CN105111206 B CN 105111206B
- Authority
- CN
- China
- Prior art keywords
- amine derivative
- crystal form
- cyclopropanecarbonyl amine
- derivative crystal
- cyclopropanecarbonyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/13—Crystalline forms, e.g. polymorphs
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention provides a kind of cyclopropanecarbonyl amine derivative crystal form E of formula (I),Its XRPD collection of illustrative plates has diffraction maximum at 2 θ=8.717,9.758,10.299,10.8,12.879,15.401,16.64,16.92,17.859,18.759,19.499,20.678,22.841,23.178,23.88,24.479,25.958,27.06,28.039,29.521,31.121, wherein 2 θ values error ranges are ± 0.2.The cyclopropanecarbonyl amine derivative crystal form E that the present invention is provided has good high-temperature stability and light durability, and with agent of low hygroscopicity and good solubility, can be in the inflammation for the treatment of or prevention JAK participations, autoimmune disease, proliferative disease, graft-rejection and congenital cartilage deformity or with being applied in the medicine of disease caused by IL6 hypersecretions, and with preferable bioavilability, the qualitative, quantitative information provided simultaneously, has great importance to the curative effect for further studying such solid drugs.
Description
Technical field
The present invention relates to a kind of polymorphic of the cyclopropanecarbonyl amine derivative as JAK inhibitor, in particular it relates to one
Plant cyclopropanecarbonyl amine derivative crystal form E and preparation method thereof.
Background technology
JAK is Janus kinases (Janus Kinase), is a kind of non-receptor type tyrosine protein kinase, is also that a class is non-
The EGFR-TK of transmembrane.Because JAK can phosphorylation cytokine receptor combined with it, and can phosphorylation it is many
The individual signaling molecule containing specific SH2 domains.JAK protein families include 4 members altogether:JAK1, JAK2, JAK3 and TYK2,
They have 7 JAK homeodomains (JAK homology domain, JH) in structure, wherein JH1 domains be kinases area,
JH2 domains are that "false" kinases area, JH6 and JH7 are receptorbinding regions.
TYK2 is the potential target spot of Immunoinflammatory Disorders, rejects research confirmation (Levy by people's science of heredity and mouse
D. with Loomis C., 1655-1658 pages of New England Journal of Medicine 357 (2007)).
JAK1 is the novel targets in Immunoinflammatory Disorders field.By JAK1 and other JAK heterodimericization, with the transducer cell factor
The pro-inflammatory signals conduction of driving.Therefore, it is contemplated that suppression JAK1 and/or other JAK is for a series of inflammatory conditions with other by JAK
The disease of the signal transduction driving of mediation has treatment benefit.
Cyclopropanecarbonyl amine derivative, chemical name N- [5- [4- [(1,1- dioxo -4- thio-morpholinyls) methyl] phenyl]
[1,2,4] triazol [1,5-A] pyridine -2- bases] cyclopropane carboxamide, as shown in formula (I),
A kind of JAK classes inhibitor compound, available for treat or prevent JAK participate in inflammation, autoimmune disease,
Proliferative disease, graft-rejection and congenital cartilage deformity or with disease caused by IL6 hypersecretions.In middle promulgated by the State Council
In bright patent CN 102105471 (WO 2010/010190), the synthetic method of the compound is disclosed;In Chinese invention patent
In CN 102482273 (WO 2010/149769), the purposes of cyclopropanecarbonyl amine derivative is disclosed.Repeat above-mentioned patent
Preparation method, obtains compound powder, is detected as amorphous state.Although as it is known by the man skilled in the art, amorphous big
Most occasions all have higher solubility and dissolution rate than crystal formation, but its is unstable, and hygroscopicity is strong, easily switch to stable
Crystal formation.Therefore, it is amorphous the problem of there is processing stability and bin stability, and in process of production, amorphous particle
Bulk density it is smaller, surface free energy is high, also easily causes cohesion, poor fluidity, elastic deformation a series of formulation problems such as by force,
Have a strong impact on the clinical drug use value of amorphous cyclopropanecarbonyl amine derivative.
It is well known that same medicine, crystal formation is different, its bioavilability may also can have difference, and it is stable in addition
Property, mobility, compressibility may also can be different, application of these physicochemical properties to medicine produces certain influence, so that shadow
Ring the curative effect of medicine.Accordingly, it would be desirable to the crystal formation of the cyclopropanecarbonyl amine derivative with superior physiochemical properties, it can have
Sharply used in medicine processing and pharmaceutical composition.The novel crystal forms for the cyclopropanecarbonyl amine derivative that the present invention is developed do not appear in the newspapers
Road.
The content of the invention
Problem to be solved by this invention is the unstability of existing cyclopropanecarbonyl amine derivative, hygroscopicity and easily turned
The problems such as stable crystal formation, is unfavorable for medicine processing and is used in pharmaceutical composition, the new crystalline substance of cyclopropanecarbonyl amine derivative
Type, the problem of providing more qualitative, quantitative information for the effectiveness study of solid drugs.
In order to solve the above-mentioned technical problem, the invention provides a kind of new crystal formation of cyclopropanecarbonyl amine derivative (with
Call in the following text " cyclopropanecarbonyl amine derivative crystal form E "), as shown in formula (I).
Its XRPD collection of illustrative plates 2 θ=8.717,9.758,10.299,10.8,12.879,15.401,16.64,16.92,
17.859、18.759、19.499、20.678、22.841、23.178、23.88、24.479、25.958、27.06、28.039、
29.521st, there is diffraction maximum at 31.121, wherein 2 θ values error ranges are ± 0.2.
According to the cyclopropanecarbonyl amine derivative crystal form E of the present invention, with substantially the same with Figure of description Fig. 1
XRPD collection of illustrative plates.
Present invention also offers a kind of method for preparing cyclopropanecarbonyl amine derivative crystal form E, comprise the following steps:In ring
With 1 in cyclopropane carboxamide derivative:20~1:40g/mL ratio adds organic solvent, suspends at room temperature, then filters, very
Sky is dried to obtain the cyclopropanecarbonyl amine derivative crystal form E of off-white powder.
In certain embodiments, the organic solvent is any one amide solvent or two or more amide solvents
With the mixed solvent of arbitrary proportion.
In some preferred embodiments, the amide-type organic solvent is DMF.
In above-mentioned steps, the ratio of cyclopropanecarbonyl amine derivative and solvent is preferably 1:30g/mL.
Present invention also offers another method for preparing cyclopropanecarbonyl amine derivative crystal form E, comprise the following steps:Will
Cyclopropanecarbonyl amine derivative is dissolved in the first organic solvent, and resulting solution, which is added in second of organic solvent, makes solid
Separate out, stand at room temperature, then filter, be dried in vacuo so as to which the cyclopropanecarbonyl amine derivative E for obtaining off-white powder is brilliant
Type.
In some preferred embodiments, the first described organic solvent is dimethyl sulfoxide.
In certain embodiments, second of organic solvent is that any one ketones solvent or two or more ketones are molten
Agent is with the mixed solvent of arbitrary proportion.
In some preferred embodiments, second of organic solvent is 2- butanone.
In above-mentioned steps, the ratio of cyclopropanecarbonyl amine derivative and the first solvent is preferably 1:20g/mL, first
The ratio for planting solvent and second of solvent is preferably 1:5.
Those of ordinary skill in the art can be carried out according to its knowledge and experience to the consumption of the inventive method agents useful for same
Adjustment, including scale up or reduce raw material dosage and adjustment solvent load, the scheme of these adjustment is also contained in the present invention
Method in.
The compound of cyclopropanecarbonyl amine derivative crystal form E with the present invention is for treatment and autoimmune disease
EGFR-TK (JAK) inhibitor.JAK is one kind of TYR kinases, JAK belong to participation inflammation, autoimmune disease,
Proliferative disease, graft-rejection and congenital cartilage deformity, or with disease caused by IL6 hypersecretions.The present invention's
Compound suppresses JAK1 and JAK2.
Therefore, the use in being used to suppress JAK medicine is being prepared the invention provides cyclopropanecarbonyl amine derivative crystal form E
On the way;And it is anti-for the inflammation for treating or preventing JAK participations, autoimmune disease, proliferative disease, graft rejection preparing
Should and congenital cartilage deformity or with the purposes in the medicine of disease caused by IL6 hypersecretions.
Present invention also offers pharmaceutical composition, its include according to the cyclopropanecarbonyl amine derivative crystal form E of the present invention with
And one or more pharmaceutically acceptable carriers, excipient or diluent.
In some embodiments of the invention, aforementioned pharmaceutical compositions further include other therapeutic agent, and described controls
Treat agent and be selected from chemotherapy or antiproliferative, antiinflammatory, immunological regulation or immunodepressant, neurotrophic factor, for treating itself
The activating agent of immunity disease, the activating agent for treating proliferative disease, the activating agent for treating graft-rejection, use
In the activating agent of congenital cartilage deformity or for treating the activating agent with disease caused by IL6 hypersecretions.
According to the present invention cyclopropanecarbonyl amine derivative crystal form E, with outstanding high-temperature stability, light durability,
Agent of low hygroscopicity and good solubility, are conducive to medicine to process and used in pharmaceutical composition, can treat or prevent JAK
Inflammation, autoimmune disease, proliferative disease, graft-rejection and the congenital cartilage deformity of participation are divided with IL6
Applied in the medicine for secreting excessive caused disease, and with preferable bioavilability, while the qualitative, quantitative information provided,
Have great importance to the curative effect for further studying such solid drugs.
Brief description of the drawings
The XRPD collection of illustrative plates for the cyclopropanecarbonyl amine derivative crystal form E that Fig. 1 provides for the present invention.
Five days high-temperature stability XRPD collection of illustrative plates of cyclopropanecarbonyl amine derivative crystal form E that Fig. 2 provides for the present invention.
The five days high wet stability XRPD collection of illustrative plates of cyclopropanecarbonyl amine derivative crystal form E that Fig. 3 provides for the present invention.
Five days light durability XRPD collection of illustrative plates of cyclopropanecarbonyl amine derivative crystal form E that Fig. 4 provides for the present invention.
Ten days high-temperature stability XRPD collection of illustrative plates of cyclopropanecarbonyl amine derivative crystal form E that Fig. 5 provides for the present invention.
The ten days high wet stability XRPD collection of illustrative plates of cyclopropanecarbonyl amine derivative crystal form E that Fig. 6 provides for the present invention.
Ten days light durability XRPD collection of illustrative plates of cyclopropanecarbonyl amine derivative crystal form E that Fig. 7 provides for the present invention.
Fig. 8 is the unbodied XRPD collection of illustrative plates of existing cyclopropanecarbonyl amine derivative.
Embodiment
In from detailed description below, aforementioned aspect of the present invention and other aspects of the present invention will be apparent.
The preparation of the cyclopropanecarbonyl amine derivative crystal form E of embodiment 1
500mg cyclopropanecarbonyl amine derivative raw materials are weighed in container, 15mL DMFs is added and (divides
Analysis is pure), ultrasonically treated 30min, off-white powder is obtained after filtering, vacuum drying at room temperature.It is 71% to weigh and calculate its yield.
The preparation of the cyclopropanecarbonyl amine derivative crystal form E of embodiment 2
500mg cyclopropanecarbonyl amine derivative raw materials are weighed in container, 10mL dimethyl sulfoxides (analysis is pure) is added, makes it
It is completely dissolved, resulting solution is added among 50mL 2- butanone (analysis is pure), has white solid precipitation, 12 is stood at room temperature
Hour, filtering, vacuum drying obtain off-white powder.It is 66% to weigh and calculate its yield.
Embodiment 3. characterizes cyclopropanecarbonyl amine derivative crystal form E by XRPD figures
The measurement of X-ray powder diffraction (XRPD) collection of illustrative plates, is penetrated using the multifunctional assembled X of Rigaku UltimaIV models
Line diffractometer is carried out, and specific collection information is as follows:Cu anodes (40kV, 40mA), °/minute of sweep speed 20, scanning range (2 θ
Scope) 3~45 °, scanning step 0.02, slit width 0.01.Using slide directly at test board compacting is to sample progress
Reason.Thereafter XRPD collection of illustrative plates uses similar measuring method.
Determine according to the methods described of embodiment 1 prepare cyclopropanecarbonyl amine derivative crystal form E XRPD collection of illustrative plates, 2 θ=
8.717、9.758、10.299、10.8、12.879、15.401、16.64、16.92、17.859、18.759、19.499、
20.678th, there is diffraction at 22.841,23.178,23.88,24.479,25.958,27.06,28.039,29.521,31.121
Peak, as shown in Figure 1.Wherein 2 θ values error ranges are ± 0.2.After testing, 2 θ values error ranges can also be ± 0.15.According to reality
The cyclopropanecarbonyl amine derivative crystal form E of the methods described of example 2 preparation is applied, its XRPD collection of illustrative plates and collection of illustrative plates shown in accompanying drawing 1 are essentially identical.
Spread out it will be understood by those skilled in the art that these diffraction maximums are not represented shown by cyclopropanecarbonyl amine derivative crystal form E
Penetrate the detailed situation at peak.2 θ values of X-ray powder diffraction figure be can with machine and with the change in sample preparation and
Change and slight change between batch, cited value is not intended as absolute value.It will also be appreciated that the relative intensity at peak may be with taking
Become to effect, therefore the intensity shown in the XRD traces contained by the present invention is exemplary, is not used to definitely compare.
The high-temperature stability of the cyclopropanecarbonyl amine derivative crystal form E of embodiment 4. is investigated
Cyclopropanecarbonyl amine derivative crystal form E sample is placed in 60 DEG C of baking ovens, sample is taken out after 5 days and 10 days and carried out
XRPD is tested (as shown in Figure 2 and Figure 5), to investigate stability of crystal form of the sample to temperature.As a result show, E is brilliant under hot conditions
Pattern product are stable.
The high humidity study on the stability of the cyclopropanecarbonyl amine derivative crystal form E of embodiment 5.
Cyclopropanecarbonyl amine derivative crystal form E sample is placed under 92.5% damp condition, sample is taken after 5 days and 10 days
Go out to carry out XRPD tests (as shown in Figure 3 and Figure 6), to investigate stability of crystal form of the sample to temperature.Test result is shown in table 1
Go out.As a result show, crystal form E sample stability is general under super-humid conditions.
The high wet stability of the cyclopropanecarbonyl amine derivative crystal form E of table 1
Sample | Color | Gain in weight |
Crystal form E | Off-white color | 0.00% |
Crystal form E after five days | Off-white color | - 3.63% |
Crystal form E after ten days | Off-white color | - 3.55% |
The light durability of the cyclopropanecarbonyl amine derivative crystal form E of embodiment 6 is investigated
Cyclopropanecarbonyl amine derivative crystal form E sample is placed under 4500lux intensities of illumination, by sample after 5 days and 10 days
Take out and carry out XRPD tests (as shown in figs. 4 and 7), to investigate stability of crystal form of the sample to temperature.As a result show, illumination bar
Crystal formation E samples are stable under part.
The unbodied preparation of the cyclopropanecarbonyl amine derivative of embodiment 7
Due to the synthetic method and Chinese invention patent CN that are used in Chinese invention patent CN 102482273
The synthetic method used in 102105471 is completely the same, therefore two according to described in Chinese invention patent CN 102482273
The method of kind, prepares cyclopropanecarbonyl amine derivative.After the organic layer containing cyclopropanecarbonyl amine derivative is obtained, by organic layer
Through anhydrous MgSO4Dry and be evaporated in vacuo.Final compound is obtained by flash chromatography or preparation HPLC after purification.
As shown in figure 8, being determined through XRPD, the final product of gained is amorphous samples.
The cyclopropanecarbonyl amine derivative crystal form E of embodiment 8 and unbodied solubility compare
Excessive crystal form E and amorphous powder are separately added into 20mL sample bottles, appropriate water is added, 24 is shaken at room temperature
After hour, sampling detection solubility.The water solubility of crystal form E is 80.75 μ g/mL, and unbodied water solubility is 100.32 μ g/
mL。
Spread out it can be seen from the results that the cyclopropanecarbonyl amine derivative crystal form E of the present invention has close to cyclopropane carboxamide
Biological unbodied solubility.
Although those skilled in the art is it should be understood that for illustrative purposes, this document describes the tool of the present invention
Body embodiment, but various modifications can be carried out to it without departing from the spirit and scope of the present invention.Therefore, it is of the invention specific
Embodiment and embodiment should not be considered as limiting the scope of the invention.The present invention is limited only by the appended claims.This Shen
Please in quote all documents be fully incorporated herein by reference.
Claims (9)
1. a kind of cyclopropanecarbonyl amine derivative crystal form E of formula (I), it is characterised in that
Its XRPD collection of illustrative plates 2 θ=8.717,9.758,10.299,10.8,12.879,15.401,16.64,16.92,17.859,
18.759、19.499、20.678、22.841、23.178、23.88、24.479、25.958、27.06、28.039、29.521、
There is diffraction maximum at 31.121, wherein 2 θ values error ranges are ± 0.2.
2. cyclopropanecarbonyl amine derivative crystal form E as claimed in claim 1, it is characterised in that it has and Figure of description
XRPD collection of illustrative plates substantially the same Fig. 1.
3. prepare the method for cyclopropanecarbonyl amine derivative crystal form E as claimed in claim 1 or 2, it is characterised in that including with
Lower step:With 1 in cyclopropanecarbonyl amine derivative:20~1:40g/mL ratio adds organic solvent, ultrasonic at room temperature
Processing, then filters, is dried in vacuo so as to obtain the cyclopropanecarbonyl amine derivative crystal form E of off-white powder,
Wherein, the organic solvent is DMF.
4. prepare the method for cyclopropanecarbonyl amine derivative crystal form E as claimed in claim 1 or 2, it is characterised in that including with
Lower step:Cyclopropanecarbonyl amine derivative is dissolved in the first organic solvent, by resulting solution add second it is organic molten
Solid is separated out in agent, is stood at room temperature, then filters, be dried in vacuo to obtain the cyclopropane carboxamide of off-white powder
Derivative crystal form E,
Wherein, the first described organic solvent is dimethyl sulfoxide, and second of organic solvent is 2- butanone.
5. cyclopropanecarbonyl amine derivative crystal form E as claimed in claim 1 or 2 is being prepared for suppressing in JAK medicine
Purposes.
6. cyclopropanecarbonyl amine derivative crystal form E as claimed in claim 1 or 2 is being prepared for treating or preventing JAK participations
Inflammation, autoimmune disease, proliferative disease, graft-rejection and congenital cartilage deformity or secreted with IL6
Purposes in the medicine of disease caused by many.
7. pharmaceutical composition, it includes cyclopropanecarbonyl amine derivative crystal form E as claimed in claim 1 or 2.
8. pharmaceutical composition as claimed in claim 7, it also includes one or more pharmaceutically acceptable carriers, excipient
Or diluent.
9. pharmaceutical composition as claimed in claim 7, it further includes other therapeutic agent, and described therapeutic agent, which is selected from, to be changed
Treat or antiproliferative, antiinflammatory, immunological regulation or immunodepressant, neurotrophic factor, for treating autoimmune disease
Activating agent, the activating agent for treating proliferative disease, the activating agent for treating graft-rejection, for congenital soft
The activating agent of bone malformation or for treating and the activating agent of disease caused by IL6 hypersecretions.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201510598698.6A CN105111206B (en) | 2015-09-18 | 2015-09-18 | A kind of cyclopropanecarbonyl amine derivative crystal form E and preparation method thereof |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201510598698.6A CN105111206B (en) | 2015-09-18 | 2015-09-18 | A kind of cyclopropanecarbonyl amine derivative crystal form E and preparation method thereof |
Publications (2)
Publication Number | Publication Date |
---|---|
CN105111206A CN105111206A (en) | 2015-12-02 |
CN105111206B true CN105111206B (en) | 2017-07-25 |
Family
ID=54659359
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201510598698.6A Active CN105111206B (en) | 2015-09-18 | 2015-09-18 | A kind of cyclopropanecarbonyl amine derivative crystal form E and preparation method thereof |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN105111206B (en) |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2018024236A1 (en) * | 2016-08-03 | 2018-02-08 | 苏州科睿思制药有限公司 | Novel crystal form of jak1-selective inhibitor, and manufacturing method and application thereof |
Family Cites Families (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JO3041B1 (en) * | 2008-07-25 | 2016-09-05 | Galapagos Nv | Novel compounds useful for the treatment of degenerative and inflammatory diseases |
TWI462920B (en) * | 2009-06-26 | 2014-12-01 | 葛萊伯格有限公司 | Novel compound useful for the treatment of degenerative and inflammatory diseases |
GB201402070D0 (en) * | 2014-02-07 | 2014-03-26 | Galapagos Nv | Pharmaceutical compositions for the treatment of inflammatory disorders |
GB201402071D0 (en) * | 2014-02-07 | 2014-03-26 | Galapagos Nv | Novel salts and pharmaceutical compositions thereof for the treatment of inflammatory disorders |
-
2015
- 2015-09-18 CN CN201510598698.6A patent/CN105111206B/en active Active
Also Published As
Publication number | Publication date |
---|---|
CN105111206A (en) | 2015-12-02 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN108383846A (en) | Ba Ruike is for Buddhist nun's A crystal forms and preparation method thereof | |
CN105753872B (en) | Two spiropiperidines or spiropyrrolidines derivatives | |
EP1832588A1 (en) | Condensed imidazole compound and use thereof | |
CN105980389B (en) | A kind of crystal form of disulfate of jak kinase inhibitor and preparation method thereof | |
CN105601635B (en) | Ba Ruike is for Buddhist nun phosphatic A crystal formations, H crystal form and I crystal and preparation method thereof | |
CN107406448B (en) | Granules of a compound in the form of a citrate salt | |
CN105218539B (en) | A kind of cyclopropanecarbonyl amine derivative B crystal form and preparation method thereof | |
CN105980390B (en) | A kind of crystal form of disulfate of jak kinase inhibitor and preparation method thereof | |
JP2023504866A (en) | Fluorine-containing heterocyclic derivative having macrocyclic structure and use thereof | |
CN106008468A (en) | Crystal form A, crystal form B and crystal form C of bemaciclib, and preparation methods thereof | |
CN105198880B (en) | A kind of cyclopropanecarbonyl amine derivative A crystal formations and preparation method thereof | |
CN105111206B (en) | A kind of cyclopropanecarbonyl amine derivative crystal form E and preparation method thereof | |
CN105566332B (en) | Ba Ruike is for Buddhist nun's trifluoroacetate A crystal formations and B crystal form and preparation method thereof | |
CN105198876B (en) | A kind of cyclopropanecarbonyl amine derivative H crystal form and preparation method thereof | |
CN105198878B (en) | A kind of cyclopropanecarbonyl amine derivative F crystal formations and preparation method thereof | |
CN105111207B (en) | A kind of cyclopropanecarbonyl amine derivative form D and preparation method thereof | |
CN105198879B (en) | A kind of cyclopropanecarbonyl amine derivative C crystal form and preparation method thereof | |
JP2024040206A (en) | Crystalline form of a compound | |
CN105198877B (en) | A kind of cyclopropanecarbonyl amine derivative G crystal formations and preparation method thereof | |
JPWO2020027225A1 (en) | Heterocyclic compound | |
JP6917910B2 (en) | (4-((3R, 4R) -3-methoxytetrahydro-pyran-4-ylamino) piperidine-1-yl) (5-methyl-6-(((2R, 6S) -6- (P-tolyl) tetrahydro) -2H-pyran-2-yl) methylamino) pyrimidine-4yl) metanone citrate | |
CN107868082A (en) | Bo Maxini mesylate A crystal formations and preparation method thereof | |
CN105308043B (en) | Crystal formation of hepatitis C medicine and preparation method thereof, its pharmaceutical composition and purposes | |
CN105503906B (en) | A kind of Triazolopyridine oxazine derivatives A crystal forms and preparation method thereof | |
WO2023109776A1 (en) | Fgfr4 inhibitor acid salt, preparation method therefor, and use thereof |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
C06 | Publication | ||
PB01 | Publication | ||
C10 | Entry into substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
CB02 | Change of applicant information |
Address after: 201207 Shanghai City, Pudong New Area Chinese (Shanghai) free trade zone fanchun Road No. 400 Building 1 layer 3 Applicant after: SHANGHAI XUANCHUANG BIOLOGICAL SCIENCE & TECHNOLOGY CO., LTD. Address before: 200072 Shanghai city Jiading District Fu Road No. 1011 A District 1309 room 3 Office Applicant before: SHANGHAI XUANCHUANG BIOLOGICAL SCIENCE & TECHNOLOGY CO., LTD. |
|
CB02 | Change of applicant information | ||
GR01 | Patent grant | ||
GR01 | Patent grant |